Kaposi's sarcoma-associated herpes-virus (KSHV) is now known to be the viral etiologic agent of Kaposi's sarcoma. In sub-Saharan Africa, the catastrophic intersection between an underlying endemic infection with KSHV and the HIV epidemic has resulted in KS becoming the most common malignancy among adults in many countries in this region as well as a growing cause of cancer in children. Despite rapid advances in KSHV virology, less is understood about KSHV epidemiology, especially in sub-Saharan Africa. What is known is that KSHV infection in Africa most commonly occurs in childhood, reaching adult level prevalence before puberty (20-60% depending on region), and that saliva is the body fluid that most commonly harbors KSHV. What is not known is specifically how KSHV is spread in Africa and how demographic, behavioral, and biologic factors influence transmission. The long-term goal of this research is to develop interventions to halt the spread of KSHV and ultimately prevent KS. The specific aims of this proposal are to: (1) Evaluate the prevalence and determinants of KSHV seropositivity in South African children and their caregivers, (2) Examine determinants of the shedding of KSHV in saliva among KSHV-infected individuals, (3) Develop quantitative measures for examining the determinants of incident KSHV infection in a longitudinal study, including the role of practices that expose children to saliva, intra- household relationships, and household characteristics;and (4) Determine the feasibility of a longitudinal study of South African children and their household members. The proposed research will utilize existing data and biological specimens previously collected by Dr. Butler and her mentors in domestic and African studies, as well as primary data collection in South Africa. The work is designed to provide the requisite preliminary data for a subsequent definitive longitudinal study of KSHV transmission in children in South Africa. The proposed training will provide Dr. Butler with the necessary skills in the population sciences, the biological sciences related to infectious diseases, and the ethical conduct of research in resource-poor settings needed for a research career that takes a multidisciplinary approach to the study of infectious diseases that affect children and their families in resource-poor countries.